Evidence for metabolic aberrations in asymptomatic persons with type 2 diabetes after initiation of simvastatin therapy.
Level 4 - case-series / case-control
Uncontrolled single-arm before-and-after study without a parallel control group.
PubMed 25683525 · doi:10.1016/j.trsl.2015.01.007
What was done
In 11 subjects with type 2 diabetes and no history of statin intolerance, previous statin therapy was withdrawn for 2 months. Baseline measurements included blood samples, vastus lateralis muscle biopsies, and resting energy expenditure (REE) assessments. Simvastatin (20 mg/day) was then administered for 1 month, followed by repeat testing of blood markers, muscle biopsy tissue (for mitochondrial function, coenzyme Q content, and gene expression), and REE.
What was found
Simvastatin reduced low-density lipoprotein cholesterol without inducing myalgias or significant elevations in serum creatine kinase. The intervention resulted in significant reductions in muscle citrate synthase activity and REE (exact numerical values not reported in abstract). Microarray and gene set enrichment analyses showed significant repression of gene sets involved in mitochondrial function and induction of gene sets involved in extracellular matrix remodeling. No significant differences were observed in CoQ content in muscle mitochondria, total muscle tissue, or circulating platelets.
Why it matters
This study demonstrates that statins can induce subclinical muscle mitochondrial perturbations and gene expression alterations in patients with type 2 diabetes even when typical myopathic symptoms and creatine kinase elevations are absent.
Limits
The study is limited by a very small sample size (n = 11), a single-arm uncontrolled before-and-after design without a placebo control, a short intervention duration of one month, and omission of exact numerical values or effect sizes in the abstract.
Cited by
- supports Muscle biopsies of individuals taking statins show mitochondrial damage even in the absence of muscle pain or elevated muscle enzymes.